Organization of cells
Eukaryotic cells contain well defined cellular
organelles such as:
Nucleus
Mitochondria
Endoplasmic reticulum
Golgi apparatus
Peroxisomes
lysosomes
MITOCHONDRIA
In electron micrographs of cells, mitochondria
appears as – rods, spheres or filamentous bodies.
Size: 0.5µm -1µm in diameter
up to 7µm in length.
FEATURES
Mitochondria has got an inner membrane and
an outer membrane. The space between these
two is called intermembranous space.
Inner membrane convolutes into cristae and
this increases its surface area.
Both the membranes have different appearance
and biochemical functions:
Biomedical importance
Inner membrane:
It surrounds the matrix.
It contains components of electron transport
system.
It is impermeable to most ions including H, Na,
ATP, GTP, CTP etc and to large molecules.
For the transport special carriers are present e.g.
adenine nucleotide carrier(ATP –ADP transport).
Complex II i.e. Succinate dehydrogenase .
Complex V i.e. ATP synthase complex.
Outer membrane:
It is permeable to most ions and molecules which
can move from the cytosol to intermembranous
space.
Matrix:
It is enclosed by the inner mitochondrial
membrane.
Contains enzymes of citric acid cycle.
Enzymes of β-oxidation of fatty acids.
Enzymes of amino acids oxidation.
Some enzymes of urea and heme synthesis.
NAD
FAD
ADP,Pi.
Mitochondrial DNA.
Mitochondrial cytochrome P450 system- it
causes:
a.Hydroxylation of cholesterol to steroid
hormones (placenta, adrenal cortex, ovaries
and testes)
b.Bile acid synthesis (liver)
c.Vitamin D formation( kidney).
Mitochondria plays a key role in aging-
Cytochrome c component of ETC plays a main
role in cell death and apoptosis.
Mitochondria have a role in its own replication-
they contain copies of circular DNA called
mitochondrial DNA, this DNA have information
for 13 mitochondrial proteins and some RNAs.
This is DNA inherited from mothers.
Most mitochondrial proteins are derived from
genes in nuclear DNA.
Mutation rate in mt DNA is 10 times more.
Mitochondrial Diseases:
i.Fatal infantile mitochondrial myopathy and
renal dysfunction
ii.MELAS(mitochondrial encephalopathy, lactic
acidosis and stroke).
i.Lebers hereditary optic neuropathy
ii.Myoclonic epilepsy
iii.Ragged red fiber disease.
Also implicated in:
Alzheimer’s disease, Parkinson’s ,
Cardiomyopathies and diabetes.
ENDOPLASMIC RETICULUM
Cytoplasm of eukaryotic cells contain a network
of interconnecting membranes. This extensive
structure is called endoplasmic reticulum.
It consists of membranes with smooth
appearance in some areas and rough appearance
in some areas-
Smooth endoplasmic reticulum and rough
endoplasmic reticulum.
Biomedical importance
Rough Endoplasmic Reticulum
These membranes enclose a lumen.
In this lumen newly synthesized proteins are
modified.
Rough appearance is due to the presence of
ribosomes attached on its cytosolic side(outer
side).
These ribosomes are involved in the biosynthesis
of proteins.
These proteins are either incorporated into the
membranes or into the organelles.
Special proteins are present that are called
CHAPERONES. Theses proteins play a role in
proper folding of proteins.
Protein glycosylation also occurs in ER i.e. the
carbohydrates are attached to the newly
synthesized proteins.
Smooth Endoplasmic Reticulum
Smooth endoplasmic reticulum is involved in
lipid synthesis.
Cholesterol synthesis
Steroid hormones synthesis.
Detoxification of endogenous and exogenous
substances.
The enzyme system involved in detoxification is
called Microsomal Cytochrome P450
monooxygenase system(xenobiotic metabolism).
ER along with Golgi apparatus is involved in
the synthesis of other organelles –lysosomes &
Peroxisomes.
Elongation of fatty acids e.g. Palmitic acid 16 C-
Stearic acid 18 C.
Desaturation of fatty acids.
Omega oxidation of fatty acids.
GOLGI APPARATUS
Golgi complex is a network of flattened smooth
membranous sacs- cisternae and vesicles.
These are responsible for the secretion of
proteins from the cells(hormones, plasma
proteins, and digestive enzymes).
It works in combination with ER.
Enzymes in golgi complex transfer carbohydrate
units to proteins to form of glycoporoteins, this
determines the ultimate destination of proteins.
Golgi is the major site for the synthesis of new
membrane, lysosomes and peroxisomes.
It plays two major roles in the membrane
synthesis:
i.It is involved in the processing of
oligosaccharide chains of the membranes (all
parts of the GA participates).
ii.It is involved in the sorting of various proteins
prior to their delivery(Trans Golgi network).
LYSOSOMES
These are responsible for the intracellular
digestion of both intra and extracellular
substances.
They have a single limiting membrane.
They have an acidic pH- 5
They have a group of enzymes called Hydrolases.
Biomedical importance
The enzyme content varies in different tissues
according to the requirement of tissues or the
metabolic activity of the tissue.
Lysosomal membrane is impermeable and
specific translocators are required.
Vesicles containing external material fuses with
lysosomes, form primary vesicles and then
secondary vesicles or digestive vacoules.
Lysosomes are also involved in autophagy.
Products of lysosomal digestion are released and
reutilised.
Indigestible material accumulates in the vesicles
called residual bodies and their material is
removed by exocytosis.
Some residual bodies in non dividing cells
contain a high amount of a pigmented substance
called Lipofuscin.
Also called age pigment or wear –tear pigment.
In some genetic disease individual lysosomal
enzymes are missing and this lead to the
accumulation of that particular substance.
Such lysosomes gets enlarged and they interfere
the normal function of the cell.
Such diseases are called lysosomal storage
diseases
Most impt is I-cell disease.
PEROXISOMES
Called Peroxisomes because of their
ability to produce or utilize H
2O
2.
They are small, oval or spherical in shape.
They have a fine network of tubules in
their matrix.
About 50 enzymes have been identified.
The number of enzymes fluctuates
according to the function of the cells.
Biomedical importance
Xenobiotics leads to the proliferation of
Peroxisomes in the liver.
Have an important role in the
breakdown of lipids, particularly long
chain fatty acids.
Synthesis of glycerolipids.
Synthesis of glycerol ether lipids.
Synthesis of isoprenoids.
Synthesis of bile.
Oxidation of D- amino acids.
Oxidation of Uric acid to allantoin
(animals)
Oxidation of Hydroxy acids which
leads to the formation of H
2
O
2.
Contain catalase enzyme, which
causes the breakdown of H
2O
2 .
Diseases associated:
Most important disease is
Zellweger Syndrome. There is
absence of functional peroxisomes.
This leads to the accumulation of
long chain fatty acids in the brain,
decreased formation of
plasmalogens, and defects of bile
acid formation.
NUCLEUS
The nucleus is the largest cellular
organelle in animals. In mammalian cells,
the average diameter of the nucleus is
approximately 6 micrometers (μm), which
occupies about 10% of the total cell
volume. The viscous liquid within it is
called nucleoplasm, and is similar in
composition to the cytosol found outside
the nucleus.
It appears as a dense, roughly
spherical organelle.
Eukaryotic cells contain a nucleus.
It has got two membranes- nuclear
envelope.
Outer membrane is continuous with the
membrane of endoplasmic reticulum.
Nuclear envelope has numerous pores.
That permit controlled movement of
particles and molecules between the
nuclear matrix and cytoplasm.
Most proteins, ribosomal subunits, and some RNAs
are transported through the pore complexes in a
process mediated by a family of transport factors
known as karyopherins. Those karyopherins that
mediate movement into the nucleus are also called
importins, while those that mediate movement out of
the nucleus are called exportins.
The space between the membranes is called the
Perinuclear space and is continuous with the RER
lumen.
the nuclear lamina, a meshwork within the nucleus
that adds mechanical support, much like the
cytoskeleton supports the cell as a whole.
Nucleus has got a major sub compartment-
nucleolus.
Deoxyribonucleic acid (DNA) is located in the
nucleus. It is the repository of genetic
information.
Present as DNA- protein complex –Chromatin,
which is organized into chromosomes.
A typical human cell contains 46 chromosomes.
To pack it effectively it requires interaction with
a large number of proteins. These are called
histones.
They order the DNA into basic structural unit
called Nucleosomes. Nucleosomes are further
arranged into more complex structures called
chromosomes
CHROMATIN:
It is the substance of chromosomes and each
chromosome represents the DNA in a condensed
form. It is the combination of DNA and proteins.
These proteins are called histones.
There are five classes of histones- H1,H2A, H2B,
H3, H4.These proteins are positively charged and
they interact with negatively charged DNA.
Two molecules each of H2A, H2B, H3 and H4
form the structural core of the
nucleosome.Around this core the segment of
DNA is Wound nearly twice.Neighboring
nucleosomes are joined by linker DNA.H1 is
associated with linker DNA
Biomedical importance
Nucleus contains the biochemical processes
involved in the Replication of DNA before mitosis.
Involved in the DNA repair.
Transcription of DNA – RNA synthesis.
Translation of DNA- Protein synthesis.
NUCLEOLUS- involved in the processing of rRNA
and ribosomal units
After being produced in the nucleolus, ribosomes
are exported to the cytoplasm where they translate
mRNA.
Antibodies to certain types of chromatin
organization, particularly nucleosomes, have
been associated with a number of
autoimmune diseases, such as
systemic lupus erythematosus, multiple sclerosis
These are known as anti-nuclear antibodies
(ANA).
Gene expression
Gene expression first involves transcription, in
which DNA is used as a template to produce RNA.
In the case of genes encoding proteins, that RNA
produced from this process is messenger RNA
(mRNA), which then needs to be translated by
ribosomes to form a protein. As ribosomes are
located outside the nucleus, mRNA produced
needs to be exported.
Polynucleated cells contain multiple nuclei.
In humans, skeletal muscle cells, called
myocytes, become polynucleated during
development; the resulting arrangement of
nuclei near the periphery of the cells allows
maximal intracellular space for myofibrils.
Multinucleated cells can also be abnormal in
humans; for example, cells arising from the
fusion of monocytes and macrophages,
known as giant multinucleated cells,
sometimes accompany inflammation and are
also implicated in tumor formation.
Since the nucleus is the site of transcription, it
also contains a variety of proteins which either
directly mediate transcription or are involved in
regulating the process. These proteins include
helicases that unwind the double-stranded DNA
molecule to facilitate access to it.
RNA polymerases that synthesize the growing
RNA molecule, topoisomerases that change the
amount of supercoiling in DNA, helping it wind
and unwind, as well as a large variety of
transcription factors that regulate expression.
Processing of pre-mRNA
Newly synthesized mRNA molecules are known
as primary transcripts or pre-mRNA. They must
undergo post-transcriptional modification in the
nucleus before being exported to the cytoplasm.
mRNA that appears in the nucleus without these
modifications is degraded rather than used for
protein translation.
The three main modifications are 5' Capping,
3' Polyadenylation, and RNA splicing.
Nuclear transport
Macromolecules, such as RNA and proteins, are
actively transported across the nuclear
membrane in a process called the Ran-GTP
nuclear transport cycle.
The entry and exit of large molecules from the
nucleus is tightly controlled by the nuclear pore
complexes. Although small molecules can enter
the nucleus without regulation, macromolecules
such as RNA and proteins require association
karyopherins called importins to enter the
nucleus and exportins to exit.
Cargo proteins that must be translocated from
the cytoplasm to the nucleus contain short amino
acid sequences known as
nuclear localization signals which are bound by
importins, while those transported from the
nucleus to the cytoplasm carry nuclear export
signals bound by exportins.
Assembly and disassembly
During its lifetime a nucleus may be broken
down, either in the process of cell division or as a
consequence of apoptosis, a regulated form of
cell death. During these events, the structural
components of the nucleus—the envelope and
lamina—are systematically degraded.
Anucleated and polynucleated cells
Although most cells have a single nucleus, some
eukaryotic cell types have no nucleus, and others
have many nuclei. This can be a normal process,
as in the maturation of mammalian red blood
cells, or a result of faulty cell division.
Anucleated cells contain no nucleus and are
therefore incapable of dividing to produce
daughter cells. The best-known anucleated cell is
the mammalian red blood cell, or erythrocyte,
which also lacks other organelles such as
mitochondria and serves primarily as a
transport vessel to ferry oxygen from the lungs
to the body's tissues.
There are two types of chromatin –Euchromatin
and Heterochromatin.
Euchromatin is the less compact DNA form, and
contains genes that are frequently expressed by
the cell. The other type, heterochromatin, is the
more compact form, and contains DNA that are
infrequently transcribed.